Multiple sclerosis medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [9]; Associate Editor(s)-in-Chief: Fahimeh Shojaei, M.D.
Overview
The predominant therapy for multiple sclerosis is disease-modifying treatment in relapsing-remitting multiple sclerosis, immunosuppressive threpay in progressive multiple sclerosis and Glucocorticoid therapy in acute exacerbation.
Medical Therapy
The predominant therapy for multiple sclerosis is:
Disease-modifying treatment of relapsing-remitting multiple sclerosis
Relapsing-remitting type of MS can be treated with disease modifying therapy (DMT) in order to reduce the rate of attack and disease progression.[1][2]
Infusion therapy:
- Natalizumab: This drug works as an antibody against alpha 4 subunit of integrin. As a result of Blood brain barrier disruption, inflammatory cells like lymphocytes and monocytes can access the brain parenchyma and start the process of inflammation and destruction. Integrin 4 is on the surface of these inflammatory cells and helps their adhesion to vascular endothelium. Based on some studies using this drug can reduce signs, symptoms and relapses of the disease.[3][4][5][6]
- Alemtuzumab: This drug is a monoclonal antibody and can cause reduction in CD52-expressing T cells, B cells, natural killer cells and monocytes. The side effects of this drug includes: infection, autoimmune disorders and infusion reaction.[7][8][9]
- Ocrelizumab: Ocrelizumab is a monoclonal antibody against CD20 causing B cells depletion.[10] It can reduce gadolinium-enhancing brain lesions on MRI of MS patients.[11]
- Mitoxantrone: This drug has serious side effects including cardiac toxicity, so it’s more like a reserve drug for patients who don’t respond to other therapies.[12]
Injectable therapies:
- Interferons: 1. Interferon beta-1b: This drug is a cytokine that can affect immune system and modulates it and cause reduction in the progression of the disease.[13][14] 2. Interferon beta-1a: Both Intramuscular and Subcutaneous interferon beta-1a can reduce disease progression, MRI lesions and acute attacks.[15][16]
- Glatiramer: Glatiramer is made from four amino acids and structurally similar to myelin basic protein. It binds to major histocompatibility complex molecules and competes with myelin antigens for T cell presentation.[17] this drug can reduce relapse rate of the disease.[18]
- Daclizumab: It is a monoclonal antibody against alpha chain of interleukin 2 receptor. It can reduce the relapses in MS patients.[19]
Oral therapies:
- Dimethyl fumarate: Fumarates is a neuroprotective and immunomodulatory drug which can reduce acute attacks and progression of multiple sclerosis.[20][21][22]
- Teriflunomide: This drug inhibits the biosynthesis of pyrimidines and reduces the interaction between antigen presenting cells and T cells.[23] teriflunomide can reduce relapse rate and disability progression of MS disease.[24][25] The most common side effects of this drug are nausea, diarrhea and elevated aminotransferase level.[24][26][27]
- Fingolimod: Fingolimod is an analog of sphingosine and can reduce lymphocyte migration and acute relapses of the disease.[28][29]
Treatment of progressive multiple sclerosis
- Studies show that immunosuppressive threpay includes Total lymphoid irradiation, cyclosporin, Methotrexate, Cladribine, Cyclophosphamide, Mitoxantrone, Azathioprine, Interferon, Corticosteroid, Intravenous immunoglobulin, Plasma exchange, bone marrow transplant, Anti-integrin antibodies (natalizumab) can be beneficial in progressive and sever case of multiple sclerosis.[30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][5]
Treatment of acute exacerbation of multiple sclerosis
- Management of acute attacks of multiple sclerosis may help patients to recover faster but has no effect in long term signs and symptoms.[45][46]
- Glucocorticoid therapy: We commonly use 500 to 1000 mg of methylprednisolone daily.[47]
- The side effects of this therapy include depression or mania, infection and GI disturbance.[48]
- Multiple studies demonstrate that plasma exchange can be beneficial in acute attacks of multiple sclerosis too.[43][49]
Symptom management
- Bladder dysfunction: Bladder dysfunction due to detresor overactivity can be treated with antimuscarinic and anticholinergic drugs such as oxybutynin, tolterodine, propantheline, propiverine, fesoterodine, and solifenacin.[50][51]
- Sexual dysfunction: The very first step in treating sexual dysfunction is to treat neuropathic or visual pain and spasticity. These are the main causes of sexual dysfunction. Phosphodiesterase-5 inhibitors can be very helpful in men with MS who have erectile dysfunction.[52][53][54]
- Cognition: Some of disease modifying treatments such as interferons, natalizumab, and fingolimod seems to have a good effect on cognitive problems in MS patients. There is some evidence of the cholinesterase inhibitors (donepezil) being beneficial to MS patients with cognitive disorders.[55][56]
- Fatigue: Drugs such as amantadine[57][58]and pemoline [59][60] as well as psychological consult [61][62] can have a good effect on reducing fatigue in MS patients.
- Internuclear ophthalmoplegia: Potassium channel blocker, like dalfampridine, can have a good effect on axonal function and improving acular adduction.[63] Botulinum injection into eye muscles can improve diplopia in some patients.[64][65]
- Optic Neuritis: Intravenous treatment with methylprednisolon may have beneficial effect on visual function.[66]
- Trigeminal Neuralgia: Some drugs such as anticonvulsants (carbamazepine[67], phenytoin[68], gabapentin[69] [70]) seems to be useful in treatment of trigeminal neuralgia.
- Lhermitte's Sign and Dysesthesias: These symptoms can be treated with carbamazepine, clonazepam, and amitriptyline.[71][72][73]
- Spasticity: Some drugs such as baclofen[74], dantrolene[75], diazepam[76], tizanidine[77][78][79] and intrathecal injections of baclofen can be beneficial.[80]
- Tremor and Ataxia: There are a list of drugs such as isoniazid[81][82][83][84], carbamazepine[85], propranolol[86][87][88] and gluthetimide,[89] which we can use to reduce the tremor and ataxia in MS patients but their effectiveness is not considerable.[90]
References
- ↑ Capra R, Cordioli C, Rasia S, Gallo F, Signori A, Sormani MP (November 2017). "Assessing long-term prognosis improvement as a consequence of treatment pattern changes in MS". Mult. Scler. 23 (13): 1757–1761. doi:10.1177/1352458516687402. PMID 28080255.
- ↑ Lizak N, Lugaresi A, Alroughani R, Lechner-Scott J, Slee M, Havrdova E, Horakova D, Trojano M, Izquierdo G, Duquette P, Girard M, Prat A, Grammond P, Hupperts R, Grand'Maison F, Sola P, Pucci E, Bergamaschi R, Oreja-Guevara C, Van Pesch V, Ramo C, Spitaleri D, Iuliano G, Boz C, Granella F, Olascoaga J, Verheul F, Rozsa C, Cristiano E, Flechter S, Hodgkinson S, Amato MP, Deri N, Jokubaitis V, Spelman T, Butzkueven H, Kalincik T (March 2017). "Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis". J. Neurol. Neurosurg. Psychiatry. 88 (3): 196–203. doi:10.1136/jnnp-2016-313976. PMID 27683916.
- ↑ Rice GP, Hartung HP, Calabresi PA (April 2005). "Anti-alpha4 integrin therapy for multiple sclerosis: mechanisms and rationale". Neurology. 64 (8): 1336–42. doi:10.1212/01.WNL.0000158329.30470.D0. PMID 15851719.
- ↑ Hynes RO (February 1987). "Integrins: a family of cell surface receptors". Cell. 48 (4): 549–54. PMID 3028640.
- ↑ 5.0 5.1 Yednock TA, Cannon C, Fritz LC, Sanchez-Madrid F, Steinman L, Karin N (March 1992). "Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin". Nature. 356 (6364): 63–6. doi:10.1038/356063a0. PMID 1538783.
- ↑ Kent SJ, Karlik SJ, Cannon C, Hines DK, Yednock TA, Fritz LC, Horner HC (April 1995). "A monoclonal antibody to alpha 4 integrin suppresses and reverses active experimental allergic encephalomyelitis". J. Neuroimmunol. 58 (1): 1–10. PMID 7730443.
- ↑ Ruck T, Bittner S, Wiendl H, Meuth SG (July 2015). "Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond". Int J Mol Sci. 16 (7): 16414–39. doi:10.3390/ijms160716414. PMC 4519957. PMID 26204829.
- ↑ Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK (October 2008). "Alemtuzumab vs. interferon beta-1a in early multiple sclerosis". N. Engl. J. Med. 359 (17): 1786–801. doi:10.1056/NEJMoa0802670. PMID 18946064.
- ↑ Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DA (November 2012). "Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial". Lancet. 380 (9856): 1819–28. doi:10.1016/S0140-6736(12)61769-3. PMID 23122652.
- ↑ Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L (January 2017). "Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis". N. Engl. J. Med. 376 (3): 221–234. doi:10.1056/NEJMoa1601277. PMID 28002679.
- ↑ Kappos L, Li D, Calabresi PA, O'Connor P, Bar-Or A, Barkhof F, Yin M, Leppert D, Glanzman R, Tinbergen J, Hauser SL (November 2011). "Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial". Lancet. 378 (9805): 1779–87. doi:10.1016/S0140-6736(11)61649-8. PMID 22047971.
- ↑ Goodin DS, Arnason BG, Coyle PK, Frohman EM, Paty DW (November 2003). "The use of mitoxantrone (Novantrone) for the treatment of multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology". Neurology. 61 (10): 1332–8. PMID 14638950.
- ↑ Kasper LH, Reder AT (August 2014). "Immunomodulatory activity of interferon-beta". Ann Clin Transl Neurol. 1 (8): 622–31. doi:10.1002/acn3.84. PMC 4184564. PMID 25356432.
- ↑ "Interferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. The IFNB Multiple Sclerosis Study Group and The University of British Columbia MS/MRI Analysis Group". Neurology. 45 (7): 1277–85. July 1995. PMID 7617182.
- ↑ "Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group". Lancet. 352 (9139): 1498–504. November 1998. PMID 9820297.
- ↑ Clanet M, Radue EW, Kappos L, Hartung HP, Hohlfeld R, Sandberg-Wollheim M, Kooijmans-Coutinho MF, Tsao EC, Sandrock AW (November 2002). "A randomized, double-blind, dose-comparison study of weekly interferon beta-1a in relapsing MS". Neurology. 59 (10): 1507–17. PMID 12451189.
- ↑ Arnon R, Aharoni R (October 2004). "Mechanism of action of glatiramer acetate in multiple sclerosis and its potential for the development of new applications". Proc. Natl. Acad. Sci. U.S.A. 101 Suppl 2: 14593–8. doi:10.1073/pnas.0404887101. PMC 521994. PMID 15371592.
- ↑ Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, Myers LW, Panitch HS, Rose JW, Schiffer RB (July 1995). "Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group". Neurology. 45 (7): 1268–76. PMID 7617181.
- ↑ Gold R, Giovannoni G, Selmaj K, Havrdova E, Montalban X, Radue EW, Stefoski D, Robinson R, Riester K, Rana J, Elkins J, O'Neill G (June 2013). "Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial". Lancet. 381 (9884): 2167–75. doi:10.1016/S0140-6736(12)62190-4. PMID 23562009.
- ↑ Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V, Dawson KT (September 2012). "Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis". N. Engl. J. Med. 367 (12): 1087–97. doi:10.1056/NEJMoa1206328. PMID 22992072.
- ↑ Gold R, Kappos L, Arnold DL, Bar-Or A, Giovannoni G, Selmaj K, Tornatore C, Sweetser MT, Yang M, Sheikh SI, Dawson KT (September 2012). "Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis". N. Engl. J. Med. 367 (12): 1098–107. doi:10.1056/NEJMoa1114287. PMID 22992073.
- ↑ Xu Z, Zhang F, Sun F, Gu K, Dong S, He D (April 2015). "Dimethyl fumarate for multiple sclerosis". Cochrane Database Syst Rev (4): CD011076. doi:10.1002/14651858.CD011076.pub2. PMID 25900414.
- ↑ Zeyda M, Poglitsch M, Geyeregger R, Smolen JS, Zlabinger GJ, Hörl WH, Waldhäusl W, Stulnig TM, Säemann MD (September 2005). "Disruption of the interaction of T cells with antigen-presenting cells by the active leflunomide metabolite teriflunomide: involvement of impaired integrin activation and immunologic synapse formation". Arthritis Rheum. 52 (9): 2730–9. doi:10.1002/art.21255. PMID 16142756.
- ↑ 24.0 24.1 O'Connor P, Wolinsky JS, Confavreux C, Comi G, Kappos L, Olsson TP, Benzerdjeb H, Truffinet P, Wang L, Miller A, Freedman MS (October 2011). "Randomized trial of oral teriflunomide for relapsing multiple sclerosis". N. Engl. J. Med. 365 (14): 1293–303. doi:10.1056/NEJMoa1014656. PMID 21991951.
- ↑ He D, Zhang C, Zhao X, Zhang Y, Dai Q, Li Y, Chu L (March 2016). "Teriflunomide for multiple sclerosis". Cochrane Database Syst Rev. 3: CD009882. doi:10.1002/14651858.CD009882.pub3. PMID 27003123.
- ↑ O'Connor PW, Li D, Freedman MS, Bar-Or A, Rice GP, Confavreux C, Paty DW, Stewart JA, Scheyer R (March 2006). "A Phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses". Neurology. 66 (6): 894–900. doi:10.1212/01.wnl.0000203121.04509.31. PMID 16567708.
- ↑ O'Connor P, Comi G, Freedman MS, Miller AE, Kappos L, Bouchard JP, Lebrun-Frenay C, Mares J, Benamor M, Thangavelu K, Liang J, Truffinet P, Lawson VJ, Wolinsky JS (March 2016). "Long-term safety and efficacy of teriflunomide: Nine-year follow-up of the randomized TEMSO study". Neurology. 86 (10): 920–30. doi:10.1212/WNL.0000000000002441. PMC 4782117. PMID 26865517.
- ↑ Cohen JA, Chun J (May 2011). "Mechanisms of fingolimod's efficacy and adverse effects in multiple sclerosis". Ann. Neurol. 69 (5): 759–77. doi:10.1002/ana.22426. PMID 21520239.
- ↑ La Mantia L, Tramacere I, Firwana B, Pacchetti I, Palumbo R, Filippini G (April 2016). "Fingolimod for relapsing-remitting multiple sclerosis". Cochrane Database Syst Rev. 4: CD009371. doi:10.1002/14651858.CD009371.pub2. PMID 27091121.
- ↑ Gonsette RE, Demonty L, Delmotte P (February 1977). "Intensive immunosuppression with cyclophosphamide in multiple sclerosis. Follow up of 110 patients for 2-6 years". J. Neurol. 214 (3): 173–81. PMID 65452.
- ↑ Hommers OR, Lamers KJ, Reekers P (1980). "Effect of intensive immunosuppression on the course of chronic progressive multiple sclerosis". J. Neurol. 223 (3): 177–90. PMID 6157011.
- ↑ Mertin J, Rudge P, Kremer M, Healey MJ, Knight SC, Compston A, Batchelor JR, Thompson EJ, Halliday AM, Denman M, Medawar PB (August 1982). "Double-blind controlled trial of immunosuppression in the treatment of multiple sclerosis: final report". Lancet. 2 (8294): 351–4. PMID 6124759.
- ↑ Cook SD, Devereux C, Troiano R, Hafstein MP, Zito G, Hernandez E, Lavenhar M, Vidaver R, Dowling PC (June 1986). "Effect of total lymphoid irradiation in chronic progressive multiple sclerosis". Lancet. 1 (8495): 1405–9. PMID 2872516.
- ↑ "Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. The Multiple Sclerosis Study Group". Ann. Neurol. 27 (6): 591–605. June 1990. doi:10.1002/ana.410270603. PMID 2193613.
- ↑ Goodkin DE, Rudick RA, VanderBrug Medendorp S, Daughtry MM, Schwetz KM, Fischer J, Van Dyke C (January 1995). "Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis". Ann. Neurol. 37 (1): 30–40. doi:10.1002/ana.410370108. PMID 7818255.
- ↑ Sipe JC, Romine JS, Koziol JA, McMillan R, Zyroff J, Beutler E (July 1994). "Cladribine in treatment of chronic progressive multiple sclerosis". Lancet. 344 (8914): 9–13. PMID 7912347.
- ↑ Hauser SL, Dawson DM, Lehrich JR, Beal MF, Kevy SV, Propper RD, Mills JA, Weiner HL (January 1983). "Intensive immunosuppression in progressive multiple sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH". N. Engl. J. Med. 308 (4): 173–80. doi:10.1056/NEJM198301273080401. PMID 6294517.
- ↑ Edan G, Miller D, Clanet M, Confavreux C, Lyon-Caen O, Lubetzki C, Brochet B, Berry I, Rolland Y, Froment JC, Cabanis E, Iba-Zizen MT, Gandon JM, Lai HM, Moseley I, Sabouraud O (February 1997). "Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria". J. Neurol. Neurosurg. Psychiatry. 62 (2): 112–8. PMC 486720. PMID 9048709.
- ↑ Yudkin PL, Ellison GW, Ghezzi A, Goodkin DE, Hughes RA, McPherson K, Mertin J, Milanese C (October 1991). "Overview of azathioprine treatment in multiple sclerosis". Lancet. 338 (8774): 1051–5. PMID 1681364.
- ↑ "Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. European Study Group on interferon beta-1b in secondary progressive MS". Lancet. 352 (9139): 1491–7. November 1998. PMID 9820296.
- ↑ Goodkin DE, Kinkel RP, Weinstock-Guttman B, VanderBrug-Medendorp S, Secic M, Gogol D, Perryman JE, Uccelli MM, Neilley L (July 1998). "A phase II study of i.v. methylprednisolone in secondary-progressive multiple sclerosis". Neurology. 51 (1): 239–45. PMID 9674809.
- ↑ Fazekas F, Deisenhammer F, Strasser-Fuchs S, Nahler G, Mamoli B (March 1997). "Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group". Lancet. 349 (9052): 589–93. PMID 9057729.
- ↑ 43.0 43.1 Weinshenker BG, O'Brien PC, Petterson TM, Noseworthy JH, Lucchinetti CF, Dodick DW, Pineda AA, Stevens LN, Rodriguez M (December 1999). "A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease". Ann. Neurol. 46 (6): 878–86. PMID 10589540.
- ↑ van Gelder M, Kinwel-Bohré EP, van Bekkum DW (March 1993). "Treatment of experimental allergic encephalomyelitis in rats with total body irradiation and syngeneic BMT". Bone Marrow Transplant. 11 (3): 233–41. PMID 8467289.
- ↑ Brusaferri F, Candelise L (June 2000). "Steroids for multiple sclerosis and optic neuritis: a meta-analysis of randomized controlled clinical trials". J. Neurol. 247 (6): 435–42. PMID 10929272.
- ↑ Lublin FD, Baier M, Cutter G (December 2003). "Effect of relapses on development of residual deficit in multiple sclerosis". Neurology. 61 (11): 1528–32. PMID 14663037.
- ↑ Kupersmith MJ, Kaufman D, Paty DW, Ebers G, McFarland H, Johnson K, Reingold S, Whitaker J (January 1994). "Megadose corticosteroids in multiple sclerosis". Neurology. 44 (1): 1–4. PMID 8290041.
- ↑ Morrow SA, Barr J, Rosehart H, Ulch S (November 2015). "Depression and hypomania symptoms are associated with high dose corticosteroids treatment for MS relapses". J Affect Disord. 187: 142–6. doi:10.1016/j.jad.2015.08.040. PMID 26334182.
- ↑ Ehler J, Koball S, Sauer M, Mitzner S, Hickstein H, Benecke R, Zettl UK (2015). "Response to Therapeutic Plasma Exchange as a Rescue Treatment in Clinically Isolated Syndromes and Acute Worsening of Multiple Sclerosis: A Retrospective Analysis of 90 Patients". PLoS ONE. 10 (8): e0134583. doi:10.1371/journal.pone.0134583. PMC 4526633. PMID 26244762.
- ↑ Yang CC (November 2013). "Bladder management in multiple sclerosis". Phys Med Rehabil Clin N Am. 24 (4): 673–86. doi:10.1016/j.pmr.2013.06.004. PMID 24314685.
- ↑ Frohman TC, Castro W, Shah A, Courtney A, Ortstadt J, Davis SL, Logan D, Abraham T, Abraham J, Remington G, Treadaway K, Graves D, Hart J, Stuve O, Lemack G, Greenberg B, Frohman EM (March 2011). "Symptomatic therapy in multiple sclerosis". Ther Adv Neurol Disord. 4 (2): 83–98. doi:10.1177/1756285611400658. PMC 3105617. PMID 21694806.
- ↑ Litwiller SE, Frohman EM, Zimmern PE (March 1999). "Multiple sclerosis and the urologist". J. Urol. 161 (3): 743–57. PMID 10022678.
- ↑ Fowler CJ, Miller JR, Sharief MK, Hussain IF, Stecher VJ, Sweeney M (May 2005). "A double blind, randomised study of sildenafil citrate for erectile dysfunction in men with multiple sclerosis". J. Neurol. Neurosurg. Psychiatry. 76 (5): 700–5. doi:10.1136/jnnp.2004.038695. PMC 1739638. PMID 15834030.
- ↑ Safarinejad MR (January 2009). "Evaluation of the safety and efficacy of sildenafil citrate for erectile dysfunction in men with multiple sclerosis: a double-blind, placebo controlled, randomized study". J. Urol. 181 (1): 252–8. doi:10.1016/j.juro.2008.09.003. PMID 19013598.
- ↑ Patti F (November 2012). "Treatment of cognitive impairment in patients with multiple sclerosis". Expert Opin Investig Drugs. 21 (11): 1679–99. doi:10.1517/13543784.2012.716036. PMID 22876911.
- ↑ Krupp LB, Christodoulou C, Melville P, Scherl WF, MacAllister WS, Elkins LE (November 2004). "Donepezil improved memory in multiple sclerosis in a randomized clinical trial". Neurology. 63 (9): 1579–85. PMID 15534239.
- ↑ Pucci E, Branãs P, D'Amico R, Giuliani G, Solari A, Taus C (2007). "Amantadine for fatigue in multiple sclerosis". Cochrane database of systematic reviews (Online) (1): CD002818. doi:10.1002/14651858.CD002818.pub2. PMID 17253480.
- ↑ Amantadine. US National Library of Medicine (Medline) (2003-04-01). Retrieved on 2007-10-07.
- ↑ Weinshenker BG, Penman M, Bass B, Ebers GC, Rice GP (1992). "A double-blind, randomized, crossover trial of pemoline in fatigue associated with multiple sclerosis". Neurology. 42 (8): 1468–71. PMID 1641137.
- ↑ Pemoline. US National Library of Medicine (Medline) (2006-01-01). Retrieved on 2007-10-07.
- ↑ Mathiowetz VG, Finlayson ML, Matuska KM, Chen HY, Luo P (2005). "Randomized controlled trial of an energy conservation course for persons with multiple sclerosis". Mult. Scler. 11 (5): 592–601. PMID 16193899.
- ↑ Matuska K, Mathiowetz V, Finlayson M (2007). "Use and perceived effectiveness of energy conservation strategies for managing multiple sclerosis fatigue". The American journal of occupational therapy. : official publication of the American Occupational Therapy Association. 61 (1): 62–9. PMID 17302106.
- ↑ Serra A, Skelly MM, Jacobs JB, Walker MF, Cohen JA (July 2014). "Improvement of internuclear ophthalmoparesis in multiple sclerosis with dalfampridine". Neurology. 83 (2): 192–4. doi:10.1212/WNL.0000000000000567. PMC 4117173. PMID 24907233.
- ↑ Murthy R, Dawson E, Khan S, Adams GG, Lee J (October 2007). "Botulinum toxin in the management of internuclear ophthalmoplegia". J AAPOS. 11 (5): 456–9. doi:10.1016/j.jaapos.2007.03.005. PMID 17498988.
- ↑ Safarpour Y, Mousavi T, Jabbari B (August 2017). "Botulinum Toxin Treatment in Multiple Sclerosis-a Review". Curr Treat Options Neurol. 19 (10): 33. doi:10.1007/s11940-017-0470-5. PMID 28819801.
- ↑ Sellebjerg F, Nielsen HS, Frederiksen JL, Olesen J (April 1999). "A randomized, controlled trial of oral high-dose methylprednisolone in acute optic neuritis". Neurology. 52 (7): 1479–84. PMID 10227638.
- ↑ Information from the USA National library of medicine on carbamazepine[1]
- ↑ Information from the USA National library of medicine on phenytoin[2]
- ↑ Information from the USA National library of medicine on gabapentin[3]
- ↑ Solaro C, Messmer Uccelli M, Uccelli A, Leandri M, Mancardi GL (2000). "Low-dose gabapentin combined with either lamotrigine or carbamazepine can be useful therapies for trigeminal neuralgia in multiple sclerosis". Eur. Neurol. 44 (1): 45–8. PMID 10894995.
- ↑ Information from the USA National library of medicine on clonazepam[4]
- ↑ Information from the USA National library of medicine on amitriptyline[5]
- ↑ Moulin DE, Foley KM, Ebers GC (1988). "Pain syndromes in multiple sclerosis". Neurology. 38 (12): 1830–4. PMID 2973568.
- ↑ ;Baclofen oral. US National Library of Medicine (Medline) (2003-04-01). Retrieved on 2007-10-17.
- ↑ Dantrolene oral. US National Library of Medicine (Medline) (2003-04-01). Retrieved on 2007-10-17.
- ↑ Diazepam. US National Library of Medicine (Medline) (2005-07-01). Retrieved on 2007-10-17.
- ↑ Tizanidine. US National Library of Medicine (Medline) (2005-07-01). Retrieved on 2007-10-17.
- ↑ Beard S, Hunn A, Wight J (2003). "Treatments for spasticity and pain in multiple sclerosis: a systematic review". Health technology assessment (Winchester, England). 7 (40): iii, ix–x, 1–111. PMID 14636486.
- ↑ Paisley S, Beard S, Hunn A, Wight J (2002). "Clinical effectiveness of oral treatments for spasticity in multiple sclerosis: a systematic review". Mult. Scler. 8 (4): 319–29. PMID 12166503.
- ↑ Becker WJ, Harris CJ, Long ML, Ablett DP, Klein GM, DeForge DA (1995). "Long-term intrathecal baclofen therapy in patients with intractable spasticity". The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques. 22 (3): 208–17. PMID 8529173.
- ↑ Bozek CB, Kastrukoff LF, Wright JM, Perry TL, Larsen TA (1987). "A controlled trial of isoniazid therapy for action tremor in multiple sclerosis". J. Neurol. 234 (1): 36–9. PMID 3546605.
- ↑ Duquette P, Pleines J, du Souich P (1985). "Isoniazid for tremor in multiple sclerosis: a controlled trial". Neurology. 35 (12): 1772–5. PMID 3906430.
- ↑ Hallett M, Lindsey JW, Adelstein BD, Riley PO (1985). "Controlled trial of isoniazid therapy for severe postural cerebellar tremor in multiple sclerosis". Neurology. 35 (9): 1374–7. PMID 3895037.
- ↑ Information from the USA National library of medicine on Isoniazid [6]
- ↑ Information from the USA National library of medicine on carbamazepine [7]
- ↑ Koller WC (1984). "Pharmacologic trials in the treatment of cerebellar tremor". Arch. Neurol. 41 (3): 280–1. PMID 6365047.
- ↑ Sechi GP, Zuddas M, Piredda M, Agnetti V, Sau G, Piras ML, Tanca S, Rosati G (1989). "Treatment of cerebellar tremors with carbamazepine: a controlled trial with long-term follow-up". Neurology. 39 (8): 1113–5. PMID 2668787.
- ↑ Information from the USA National library of medicine on propanolol[8]
- ↑ Aisen ML, Holzer M, Rosen M, Dietz M, McDowell F (1991). "Glutethimide treatment of disabling action tremor in patients with multiple sclerosis and traumatic brain injury". Arch. Neurol. 48 (5): 513–5. PMID 2021365.
- ↑ Mills RJ, Yap L, Young CA (2007). "Treatment for ataxia in multiple sclerosis". Cochrane database of systematic reviews (Online) (1): CD005029. doi:10.1002/14651858.CD005029.pub2. PMID 17253537.